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Synthesis, characterization and in vitro biological activities of ruthenium(II) polypyridyl complexes

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Abstract

The ruthenium(II) polypyridyl complexes [Ru(dmb)2(TCPI)](PF6)2 (1) and [Ru(ttbpy)2(TCPI)](PF6)2 (2) (dmb = 4,4′-dimethyl-2,2′-bipyridine, TCPI = 2-(3-(1H-1,3,7,8-tetraazacyclopenta[l]phenanthren-2-yl)phenyl)benzo[de]isoquinoline-1,3-dione, ttbpy = 4,4′-ditertiary butyl-2,2′-bipyridine) were synthesized and characterized. The in vitro cytotoxicities of the complexes were examined against a panel of cancer cell lines including SGC-7901, PC-12, HepG-2, SiHa, Eca-109, HeLa, Eca-9706, HOS and LO2 by 3-(4,5-dimethylthiazole)-2,5-diphenyltetrazolium bromide (MTT) method. Both complexes show higher activities against PC-12 cells, with IC50 values of 34.4 ± 1.3 and 26.8 ± 2.4 μM for 1 and 2, respectively. Cell apoptosis was assayed with acridine orange (AO) and ethidium bromide (EB) and annexin V/PI staining methods using fluorescence microscopy and flow cytometry. The reactive oxygen species, mitochondrial membrane potential and cell cycle distribution were assessed. Cell invasion was determined by Matrigel invasion assay, and the proteins associated with cell apoptosis were analyzed by western blot. The results suggest that the complexes induce the apoptosis of PC-12 cells through a ROS-mediated mitochondrial dysfunction pathway, accompanied by regulation of the expression of caspases and Bcl-2 family proteins.

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References

  1. Milacic V, Chen D, Ronconi L, Landis-Piwowar KR, Fregona D, Dou QP (2006) Cancer Res 66:10478–10486

    Article  CAS  Google Scholar 

  2. Kostova I (2006) Anticancer Agents Med Chem 6:19–32

    Article  CAS  Google Scholar 

  3. Fuertes MA, Alonso C, Perez JM (2003) Chem Rev 103:645–662

    Article  CAS  Google Scholar 

  4. Jung Y, Lippard SJ (2007) Chem Rev 107:1387–1407

    Article  CAS  Google Scholar 

  5. Wang D, Lippard SJ (2005) Nat Rev Drug Discov 4:307–320

    Article  CAS  Google Scholar 

  6. Bruijnincx PCA, Sadler PJ (2008) Curr Opin Chem Biol 12:197–206

    Article  CAS  Google Scholar 

  7. Lai SH, Li W, Wang XZ, Zhang C, Zeng CC, Tang B, Wan D, Liu YJ (2016) RSC Adv 6:63143–63155

    Article  CAS  Google Scholar 

  8. Zhao ZN, Luo ZD, Wu Q, Zheng WJ, Feng YX, Chen TF (2014) Dalton Trans 43:17017–17028

    Article  CAS  Google Scholar 

  9. Luo ZD, Yu LL, Yang F, Zhao ZN, Yu B, Lai HQ, Wong KH, Ngai SM, Zheng WJ, Chen TF (2014) Metallomics 6:1480–1490

    Article  CAS  Google Scholar 

  10. Gao EJ, Sun N, Zhang SZ, Ding YQ, Qiu X, Zhan Y, Zhu MC (2016) Eur J Med Chem 121:1–11

    Article  CAS  Google Scholar 

  11. Bergamo A, Gaiddon C, Schellens JH, Beijnen JH, Sava G (2012) J Inorg Biochem 106:90–99

    Article  CAS  Google Scholar 

  12. Ang WH, Dyson PJ (2006) Eur J Med Chem 20:4003–4018

    Google Scholar 

  13. Reisner E, Arion VB, Keppler BK, Pombeiro AJ (2008) Inorg Chim Acta 361:1569–1583

    Article  CAS  Google Scholar 

  14. Li W, Han BJ, Yao JH, Jiang GB, Liu YJ (2015) RSC Adv 5:24534–24543

    Article  CAS  Google Scholar 

  15. Liu JP, Chen Y, Li GY, Zhang PY, Jin CZ, Zeng LL, Ji LN, Chao H (2015) Biomaterials 56:140–153

    Article  CAS  Google Scholar 

  16. Zhang C, Zeng CC, Lai SH, Xing DG, Li W, Han BJ, Liu YJ (2016) Polyhedron 106:115–124

    Article  CAS  Google Scholar 

  17. Mazuryk O, Suzenet F, Kieda C, Brindell M (2015) Metallomics 7:553–566

    Article  CAS  Google Scholar 

  18. Xie YY, Huang HL, Yao JH, Lin GJ, Jiang GB, Liu YJ (2013) Eur J Med Chem 63:603–610

    Article  CAS  Google Scholar 

  19. Zhang Y, Hu PC, Cai P, Yang F, Cheng GZ (2015) RSC Adv 5:11591–11594

    Article  CAS  Google Scholar 

  20. Jiang GB, Zheng X, Yao JH, Han BJ, Li W, Wang J, Huang HL, Liu YJ (2014) J Inorg Biochem 14:170–179

    Article  Google Scholar 

  21. Yu QQ, Liu YN, Xu L, Zheng CP, Le FL, Qin XY, Liu YY, Liu J (2014) Eur J Med Chem 82:82–95

    Article  CAS  Google Scholar 

  22. Lai SH, Jiang GB, Yao JH, Li W, Han BJ, Zhang C, Zeng CC, Liu YJ (2015) J Inorg Biochem 152:1–9

    Article  CAS  Google Scholar 

  23. Xu L, Liu YY, Chen LM, Xie YY, Liang JX, Chao H (2016) J Inorg Biochem 159:82–88

    Article  CAS  Google Scholar 

  24. Xia Y, Chen QC, Qin YY, Sun DD, Zhang JN, Liu J (2013) N J Chem 37:3706–3715

    Article  CAS  Google Scholar 

  25. Lai SH, Li W, Yao JH, Han BJ, Jiang GB, Zhang C, Zeng CC, Liu YJ (2016) J Photochem Photobiol B Biol 158:39–48

    Article  CAS  Google Scholar 

  26. Pena B, David A, Pavani C, Baptista MS, Pellois JP, Turro C, Dunbar KM (2014) Organometallics 33:1100–1103

    Article  CAS  Google Scholar 

  27. Sullivan BP, Salmon DJ, Meyer TJ (1978) Inorg Chem 17:3334–3341

    Article  CAS  Google Scholar 

  28. Zeng CC, Zhang C, Lai SH, Yin H, Tang B, Wan D, Liu YJ (2016) Inorg Chim Commun 70:210–218

    Article  CAS  Google Scholar 

  29. Mosmann T (1983) J Immunol Methods 65:55–63

    Article  CAS  Google Scholar 

  30. Zaidman BZ, Yassin M, Mahajna J, Wasser SP (2005) Appl Microbiol Biotechnol 67:453–468

    Article  CAS  Google Scholar 

  31. Li WJ, Chen Y, Nie SP, Xie MY, He M, Zhang SS, Zhu KX (2011) J Cell Biochem 112:860–871

    Article  CAS  Google Scholar 

  32. Taraphdar AK, Roy M, Bhattacharya RK (2001) Curr Sci 80:1387–1396

    CAS  Google Scholar 

  33. Royall JA, Ischiropoulos H (1993) Arch Biochem Biophys 302:348–355

    Article  CAS  Google Scholar 

  34. Capella MAM, Capella LS, Valente RC, Gefé M, Lopes AG (2007) Cell Biol Toxicol 23:413–423

    Article  CAS  Google Scholar 

  35. Qin Y, Lu M, Gong X (2008) Cell Biol Int 32:224–228

    Article  CAS  Google Scholar 

  36. León IE, Di Virgilio AL, Barrio AD, Arrambide G, Gambino D, Etcheverry SB (2012) Metallomics 4:1287–1296

    Article  Google Scholar 

  37. Silveira LR, Pereira-Da-Silva L, Juel C, Hellsten Y (2003) Free Radical Biol Med 35:455–464

    Article  CAS  Google Scholar 

  38. Ito K, Hirao A, Arai F, Takubo K, Matsuoka S, Miyamoto K, Ohmura M, Naka K, Hosokawa K, Ikeda Y, Suda T (2006) Nat Med 12:446–451

    Article  CAS  Google Scholar 

  39. Thornberry NA, Rano TA, Peterson EP, Rasper DM, Timkey T, Garcia-Calvo M, Houtzager VM, Nordstrom PA, Roy S, Vaillancourt JP, Chapman KT, Nicholson DWA (1997) J Biol Chem 272:17907–17911

    Article  CAS  Google Scholar 

  40. Shats I, Milyavsky M, Tang X, Stambolsky P, Erez N, Brosh R, Kogan I, Braunstein I, Tzukerman M, Ginsberg D, Rotter V (2004) J Biol Chem 279:50976–50985

    Article  CAS  Google Scholar 

  41. Chou CC, Yang JS, Lu HS, Ip SW, Lo C, Wu CC, Lin JP, Tang NY, Chung JG, Chou MJ, Teng YH, Chen DR (2010) Arch Pharm Res 33:1181–1191

    Article  CAS  Google Scholar 

  42. Friedl P, Wolf K (2003) Nat Rev Cancer 3:362–374

    Article  CAS  Google Scholar 

  43. Daniel PT, Schulze-Osthoff K, Belka C, Guner D (2003) Essays Biochem 39:73–88

    Article  CAS  Google Scholar 

  44. Reed JC (1997) Semin Hematol 34:9–19

    CAS  Google Scholar 

  45. Adams JM (2003) Genes Dev 17:2481–2495

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the Natural Science Foundation of Guangdong Province (No. 2016A030313728), the High-Level Personnel Project of Guangdong Province in 2013 and the Joint Nature Science Fund of the Department of Science and Technology and the First Affiliated Hospital of Guangdong Pharmaceutical University (No. GYFYLH201315) and Project of innovation for enhancing Guangdong Pharmaceutical University, provincial experimental teaching demonstration center of chemistry & chemical engineering.

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Authors and Affiliations

  1. School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, People’s Republic of China

    Chuan-Chuan Zeng, Cheng Zhang, Shang-Hai Lai, Bing Tang, Dan Wan & Yun-Jun Liu

  2. Guangdong Cosmetics Engineering & Technology Research Center, Guangzhou, 510006, People’s Republic of China

    Yun-Jun Liu

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  1. Chuan-Chuan Zeng
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  2. Cheng Zhang
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Correspondence to Yun-Jun Liu.

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Zeng, CC., Zhang, C., Lai, SH. et al. Synthesis, characterization and in vitro biological activities of ruthenium(II) polypyridyl complexes. Transit Met Chem 41, 923–931 (2016). https://doi.org/10.1007/s11243-016-0096-6

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  • DOI: https://doi.org/10.1007/s11243-016-0096-6

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